NM_006303.4:c.136-1491G>A

Variant names:

• chr7-6013655-G-A
• rs1860460
• NM_006303.4:c.136-1491G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006303.4(AIMP2):​c.136-1491G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.652 in 152,000 control chromosomes in the GnomAD database, including 33,083 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.65 (33083 hom., cov: 32)
• Consequence: AIMP2 NM_006303.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670
• Publications: 14 publications found

Genes affected

AIMP2 (HGNC:20609): (aminoacyl tRNA synthetase complex interacting multifunctional protein 2) The protein encoded by this gene is part of the aminoacyl-tRNA synthetase complex, which contains nine different aminoacyl-tRNA synthetases and three non-enzymatic factors. The encoded protein is one of the non-enzymatic factors and is required for assembly and stability of the complex. [provided by RefSeq, May 2016]

AIMP2 Gene-Disease associations (from GenCC):

• leukodystrophy, hypomyelinating, 17

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Illumina, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AIMP2	NM_006303.4	c.136-1491G>A		intron_variant	Intron 1 of 3	ENST00000223029.8	NP_006294.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AIMP2	ENST00000223029.8	c.136-1491G>A		intron_variant	Intron 1 of 3	1	NM_006303.4	ENSP00000223029.3
AIMP2	ENST00000395236.2	c.135+4157G>A		intron_variant	Intron 1 of 2	2		ENSP00000378658.2
AIMP2	ENST00000400479.6	c.-250-1247G>A		intron_variant	Intron 1 of 4	5		ENSP00000383327.2
AIMP2	ENST00000415999.1	n.*450+515G>A		intron_variant	Intron 2 of 2	3		ENSP00000392519.1

Frequencies

GnomAD3 genomes AF: 0.652 AC: 99068 AN: 151882 Hom.: 33077 Cov.: 32

Gnomad AFR AF: 0.528

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.887

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.703

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.677

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.652 AC: 99109 AN: 152000 Hom.: 33083 Cov.: 32 AF XY: 0.654 AC XY: 48587 AN XY: 74288

African (AFR) AF: 0.527 AC: 21867 AN: 41454

American (AMR) AF: 0.599 AC: 9129 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 2777 AN: 3470

East Asian (EAS) AF: 0.886 AC: 4588 AN: 5176

South Asian (SAS) AF: 0.765 AC: 3690 AN: 4826

European-Finnish (FIN) AF: 0.703 AC: 7423 AN: 10558

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.697 AC: 47350 AN: 67956

Other (OTH) AF: 0.678 AC: 1427 AN: 2106

Alfa AF: 0.683 Hom.: 58712

Bravo AF: 0.636

Asia WGS AF: 0.772 AC: 2685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.77
DANN	Benign	0.68
PhyloP100		-0.67
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1860460; hg19: chr7-6053286;